Ras and Ras mutations in cancer

Ras genes are pre-eminent genes that are frequently linked with cancer biology. The functional loss of ras protein caused by various point mutations within the gene, is established as a prognostic factor for the genesis of a constitutively active Ras-MAPK pathway leading to cancer. Ras signaling circuit follows a complex pathway, which connects many signaling molecules and cells. Several strategies have come up for targeting mutant ras proteins for cancer therapy, however, the clinical benefits remain insignificant. Targeting the Ras-MAPK pathway is extremely complicated due its intricate networks involving several upstream and downstream regulators. Blocking oncogenic Ras is still in latent stage and requires alternative approaches to screen the genes involved in Ras transformation. Understanding the mechanism of Ras induced tumorigenesis in diverse cancers and signaling networks will open a path for drug development and other therapeutic approaches.     

Production and characterisation of monoclonal antibodies to an Indian isolate of peste des petits ruminants virus

Nine monoclonal antibodies (Mabs) were produced against an Indian isolate of peste des petits ruminants (PPR) virus. These Mabs were directed against the nucleo (N) protein and were of IgG1 isotype. The Mabs produced intranuclear or coarse granular cytoplasmic fluorescence in PPR virus infected Vero cells and did not exhibit any neutralising activity. The Mabs cross-reacted with five other local isolates of PPR virus in slot blot hybridisation, radio immunoprecipitation assay (RIPA) and fixed-cell enzyme linked immunosorbent assay (ELISA). Two of the nine Mabs cross-reacted mildly with the vaccine strain of rinderpest (RP) virus in slot blot hybridisation and fixed-cell ELISA but did not precipitate the N protein of RP virus in RIPA. The N protein specific Mabs will be highly useful in differential diagnosis of PPR from RP.     

Prairie dog presence affects occurrence patterns of disease vectors on small mammals

Wildlife disease is recognized as a burgeoning threat to imperiled species and aspects of host and vector community ecology have been shown to have significant effects on disease dynamics. The black‐tailed prairie dog is a species of conservation concern that is highly susceptible to plague, a flea‐transmitted disease. Prairie dogs (Cynomys) alter the grassland communities in which they exist and have been shown to affect populations of small rodents, which are purported disease reservoirs. To explore potential ecological effects of black‐tailed prairie dogs on plague dynamics, we quantified flea occurrence patterns on small mammals in the presence and absence of prairie dogs at 8 study areas across their geographic range. Small mammals sampled from prairie dog colonies showed significantly higher flea prevalence, flea abundance, and relative flea species richness than those sampled from off‐colony sites. Successful plague transmission likely is dependent on high prevalence and abundance of fleas that can serve as competent vectors. Prairie dogs may therefore facilitate the maintenance of plague by increasing flea occurrence on potential plague reservoir species. Our data demonstrate the previously unreported ecological influence of prairie dogs on vector species assemblages, which could influence disease dynamics.     

Temperature and Photoperiod Influence Postharvest Needle Abscission of Selected Balsam Fir (Abies balsamea L. (Mill.)) Genotypes by Modulating ABA Levels

Seasonal changes in the concentration of abscisic acid (ABA) in current-year needles of two different genotypes (AB-NSD-004 and AB-NSD-184) were monitored in branches collected from 20-year-old balsam fir (Abies balsamea L. (Mill.)) trees over a period of 11 months. A significant genotype × harvesting time interaction was observed for endogenous ABA levels and postharvest needle retention duration (NRD). A consistent pattern of seasonal variation in ABA concentration was observed in both genotypes, with the highest amount of ABA (7,887 ng g^?1 DW) accumulating in April and May. The highest levels of ABA coincided with the lowest postharvest NRD regardless of genotype. Nevertheless, genotypes differed in their ABA concentrations. Branches of genotype AB-NSD-184 sampled during August exhibited 170 days of NRD whereas those collected in May and June registered the lowest NRD of around 40 days. There was a significant negative correlation (P < 0.05) between endogenous ABA concentrations and postharvest NRD in genotype AB-NSD-184. Also, an inverse relationship was observed between the average daily photoperiod and the postharvest NRD (R ² = 0.35; P = 0.000) in the same genotype. Together with average daily temperature, the R ² value for this correlation reached the highest (0.75; P ≤ 0.00). Genotypes differed in their physiological responses to environmental cues and thus differed in their postharvest qualities. Average daily photoperiod and maximum daily temperature are strongly linked to the postharvest NRD through modulating endogenous ABA concentration.     

The Role of Carboxy-Terminal Glycosaminoglycan-binding Domain of Vitronectin in Cytoskeletal Organization and Migration of Endothelial Cells

Vitronectin is a major cell adhesion molecule present in the subendothelial matrix that mediates the attachment and spreading of a variety of cells. The carboxy-terminal end of vitronectin has a consensus sequence for glycosaminoglycan-binding. To define the functional role of this domain, we generated fragments of vitronectin that lack the glycosaminoglycan-binding domain by formic acid cleavage of plasma-derived vitronectin. In addition, we also generated similar recombinant fragments of vitronectin as glutathione S-transferase fusion proteins in E. coll. These fragments were tested for their ability to support the adhesion of human umbilical vein endothelial cells. These fragments promoted endothelial cell adhesion, reaching half maximal activity at 2-5 μg/well compared to plasma-derived vitronectin which reached at 0.2 μg/well. However, the cells that adhered to these fragments did not develop well-formed focal adhesion plaques and actin stress fibers. In addition, these fragments were poorly chemotactic for endothelial cell migration when compared to intact plasma-derived vitronectin in a modified Boyden chamber assay. The present studies show that carboxy-terminal glycosaminoglycan-binding domain of vitronectin is essential for proper cytoskeletal organization and migration of endothelial cells on vitronectin substratum.